Pyridine → Tert-butyl 3-(5-(5-bromo-3-phenoxypyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)pyrrolidine-1-carboxylate

HRID 1806187Notes

Reaction equation

HRID 1806187 reaction equation
Cl[C:2](=[N:15]OS(C)(=O)=O)[CH:3]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1.N1C=CC=CC=1.[N:27]([Na])=[C:28]=[S:29].[Br:31][C:32]1[CH:33]=[C:34]([O:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:35]([NH2:38])=[N:36][CH:37]=1>O.C(#N)C>[Br:31][C:32]1[CH:33]=[C:34]([O:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:35]([NH:38][C:28]2[S:29][N:15]=[C:2]([CH:3]3[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:4]3)[N:27]=2)=[N:36][CH:37]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 459261405-Bromo-3-phenoxypyridin-2-amineHCID 86631534Tert-butyl 3-(chloro(methylsulfonyloxyimino)methyl)pyrrolidine-1-carboxylateHCID 178507096HCID 178507096, compound

Product 1

HCID 57742930Tert-butyl 3-(5-(5-bromo-3-phenoxypyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A 40 mL flask was charges with tert-butyl 3-(chloro(methylsulfonyl-oxyimino)methyl)pyrrolidine-1-carboxylate (1.60 g, 4.90 mmol) and acetonitrile (25 mL). Added pyridine (1.22 mL, 15.1 mmol) and isothiocyanatosodium (0.398 g, 4.90 mmol) and heated to 40° C. for 45 minutes. Added 5-bromo-3-phenoxypyridin-2-amine (1.00 g, 3.77 mmol) and heated at 60° C. overnight. The reaction was cooled to ambient temperature, poured into water and extracted with EtOAc (100 mL). The organic layer were dried with sodium sulfate, filtered and concentrated. The residue was purified by MPLC (Biotage) eluting with 3:1 hexane:ethyl acetate to afford tert-butyl 3-(5-(5-bromo-3-phenoxypyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)pyrrolidine-1-carboxylate as a light yellow/off white solid: 1H NMR (d6-DMSO) δ 12.21 (s, 1H), 8.34 (s, 1H), 7.48 (s, 1H), 7.39 (t, 2H), 7.18 (t, 1H), 7.07 (d, 2H), 3.42-3.63 (m, 3H), 3.36 (m, 1H), 2.02-2.21 (m, 3H), 1.35 (s, 9H).

Workup

  1. customA 40 mL flask was
  2. extractionextracted with EtOAc (100 mL)
  3. dry with materialThe organic layer were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by MPLC (Biotage)
  7. washeluting with 3:1 hexane

Sources & evidence

ORD record
ord-bb49b04aec714fd48e3714346b2de6be
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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